Gastrointestinal (GI) cancers represent 26% of the global cancer incidence and more than one-third of all cancer-related deaths [1]. Patients with upper GI cancers have a higher risk of venous thromboembolism than patients with other malignancies [2].
GI cancers are highly invasive and metastatic, and in many cases, they are associated with a poor prognosis. Innovative and wide-ranging treatments have been developed over the years, but their efficacy differs among individuals [3]. For these reasons, there is a great need for new prognostic biomarkers for the prediction of survival and predictive biomarkers for treatment efficacy or toxicity.
The study
A recent study analyzed a large prospective cohort of patients with newly diagnosed metastatic GI cancer enrolled in the ongoing multicenter observational HYPERCAN study (NCT02622815) [4] to evaluate the capability of plasma hemostatic biomarkers (measured before starting chemotherapy) to predict early disease progression at 6 months and 1-year overall survival (OS) [5].
The study population included 626 newly diagnosed metastatic GI patients from eight Italian oncology units enrolled between May 2012 and November 2019 in the HYPERCAN study [5].
Inclusion criteria were:
- Newly diagnosed metastatic colorectal cancer (CRC) or gastric cancer (GC), stage TXNXM1
- Being a candidate for systemic chemotherapy
Exclusion criteria were:
- Acute medical illnesses
- Hospitalization
- Therapeutic anticoagulation
- Life expectancy <3 months
The study population included 462 CRC and 164 GC with a median age of 66 years (range: 26–87 years), 61% of which were male.
The analysis wanted to unveil if prechemotherapy values of hypercoagulation biomarkers and endogenous thrombin potential (ETP) may be predictive for disease progression at 6 months and 1-year OS [5].
Results
Disease progression at 6 months was observed in 25.6% of patients with metastatic GI, more in GC (46.2%) than CRC (18.8%).
The multivariate model, stratified for age, site of tumor, and number of metastases, identified D-dimer >420 ng/mL (Subdistribution Hazard Ratio, SHR = 1.4, 95% CI: 1.1–2.1; p=0.047) and ETP >1700 nM·min (SHR = 1.6, 95% CI: 1.1–2.2; p=0.014) as independent risk factors for disease progression at 6 months [5].
During the first year of follow-up, a total of 139 deaths were recorded, providing a 75.2% overall survival, with a better prognosis in CRC patients compared to GC (83.0% vs 51.1%). Again, elevated values of D-dimer and ETP were independent risk factors for 1-year OS [5].
Limitations
Data on the type of chemotherapy, molecular markers (HER-2), and genetic mutations (KRAS, NRAS, and BRAF) were unavailable for all patients and were not included in the analysis. In addition, biomarker measurements are single-point and not repeated during follow-up [5].
Conclusions
D-dimer and ETP can help identify patients at high risk for disease progression at 6 months and death. These predictors could improve the prognosis evaluation of patients with cancer, providing useful information on the type and intensity of the anticancer treatment to be administered [5].
References
- Arnold M, Abnet CC, Neale RE, et al. Global Burden of 5 Major Types of Gastrointestinal Cancer. Gastroenterology. 2020;159(1):335-349.e15. doi:10.1053/j.gastro.2020.02.068
- Young AM, Marshall A, Thirlwall J, et al. Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D). J Clin Oncol. 2018;36(20):2017-2023.
- Ulrich CM, Himbert C, Holowatyj AN, Hursting SD. Energy balance and gastrointestinal cancer: risk, interventions, outcomes and mechanisms. Nat Rev Gastroenterol Hepatol. 2018;15(11):683-698. doi:10.1038/s41575-018-0053-2
- Falanga A, Santoro A, Labianca R, et al. Hypercoagulation screening as an innovative tool for risk assessment, early diagnosis and prognosis in cancer: the HYPERCAN study. Thromb Res. 2016;140 Suppl 1:S55-S59. doi:10.1016/S0049-3848(16)30099-8
- Giaccherini C, Verzeroli C, Russo L, et al. Thrombin Generation and D-Dimer for Prediction of Disease Progression and Mortality in Patients with Metastatic Gastrointestinal Cancer. Cancers (Basel). 2022;14(18):4347. doi:10.3390/cancers14184347